The long-term goal of the proposed research is to characterize the regulation of renal sodium excretion. The broad objective of the current proposal is to determine the relationship between peritubule capillary dynamics and sodium reabsorption. Our working hypothesis is that increased renal interstitial hydrostatic pressure decreases sodium chloride reabsorption by the loop of Henle. Renal vasodilators with differing characteristics will be used as tools to discern the relationships between physical factors in the peritubular microcirculation and interstitium and subsequent effects on sodium reabsorption. The microcirculation and single nephron reabsorption of sodium will be studied utilizing micropuncture techniques primarily in rats. The specific questions to be addressed are: 1) What is the mechanism for peritubular capillary uptake of reabsorbate in the presence of renal vasodilators? 2) Why do some renal vasodilators increase renal interstitial hydrostatic pressure and sodium excretion while others do not? 3) What tubular site(s) is affected by changes in interstitial hydrostatic pressure mediated by vasodilators? 4) Is there a cause and effect relationship between changes in interstitial hydrostatic pressure and changes in sodium reabsorption? 5) What is the role of washout of the medullary concentration gradient in the natriuresis associated with renal vasodilation? Answers to these questions shold provide an understanding of the relationship between the renal circulation and sodium excretion. Specifically, the role of renal interstitial hydrostatic pressure as an important intrarenal mechanism for the regulation of sodium excretion, such as in the escape from the salt-retaining effects of mineralocorticoids, will be clarified. This is turn should provide a fundamental link in the pathophysiology of diseases characterized by abnormal sodium metabolism such as congestive heart failure and hypertension.